Despite many available methods of treatment, cardiovascular disease is one the major causes of death each year in the U.S. Thus, there is still a need for more effective agents to prevent and treat cardiac tissue injury, especially cardiac tissue injury resulting from ischemia/reperfusion.
The Nell1 gene codes for a secreted trimeric protein that stimulates bone and cartilage precursor cells (osteoblasts and chondrocytes) to differentiate into mature bone and cartilage tissue (Zhang et al., 2002; Desai et al., 2006). Nell-1 is a protein kinase C (PKC) β-binding protein. The Nell1 cDNA and amino acid sequences from a variety of mammalian species, including human, rat and mouse, have been reported.
Overexpression of Nell1 has been reported to cause premature fusion of the growing cranial bone fronts, resulting in craniosynostosis in humans and transgenic mice carrying a rat Nell1 transgene. A Nell1 knock-out mouse was also shown to exhibit several bone- and cartilage-related defects. There has been no characterization, however, of the impact of Nell1, if any, on cardiovascular development.